Tolterodine is an effective and safe compound for treatment of overactive bladder. The synthesis of tolterodine and its utility for the treatment of overactive bladder is disclosed in U.S. Pat. No. 5,382,600 (Pharmacia & Upjohn AB). An optimal efficacy/side effect profile is obtained at an oral dosage of 1 or 2 mg twice daily. The high potency (and thereby low clinically effective serum concentrations) and the relatively short half-life (about 2 hours in the majority of the population, i.e. in extensive metabolisers, EMs) makes tolterodine a possible candidate for a patch formulation. Further properties supporting the feasibility of the patch principle are that the overactive bladder is a syndrome that might benefit of a flat serum concentration profile and that antimuscarinic compounds are not known to cause tolerance.
Tolterodine has a molecular weight of 325.0 and 475.6 as the tartrate salt. The enantiomeric purity is >99%. The pKa value is 9.87 and the solubility in water is about 11 mg/ml (room temperature). The partition coefficient (Log P) between n-octanol and phosphate buffer at pH 7.32 is 1.83. 